EFFECTS OF ASN(87) AND ASP(318) MUTATIONS ON LIGAND-BINDING AND SIGNAL-TRANSDUCTION IN THE RAT GNRH RECEPTOR

被引:33
作者
COOK, JV
FACCENDA, E
ANDERSON, L
COUPER, GG
EIDNE, KA
TAYLOR, PL
机构
[1] MRC Reproductive Biology Unit, Centre for Reproductive Biology, Edinburgh EH3 9EW
关键词
D O I
10.1677/joe.0.139R001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The gonadotrophin-releasing hormone (GnRH) receptor is unlike other G-protein coupled receptors in that the highly conserved amino acids, Asp in the second transmembrane region and Asn in the seventh, are interchanged. Site-directed mutagenesis studies mutated these residues back to their normally conserved positions. Two single mutants Asn(87)Asp & Asp(318)Asn and one double mutant Asn(87)Asp Asp(318)Asn were transiently expressed in COS-I cells and their effect on binding to GnRH and inositol phosphate production measured. The single mutant Asp(318)Asn had no effect on ligand binding but abolished GnRH-dependent inositol phosphate production, whereas mutations Asn(87)Asp and Asn(87)Asp Asp(318)Asn show a complete loss of GnRH binding and subsequent inactivation of its second messenger system.
引用
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页码:R1 / R4
页数:4
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